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I think the point they were trying to make was that 'primary ischemic' (i.e., CCSVI) was more likely than WD.

I can get behind that!

I am concerned about the Wallerian degeneration, since it's listed as one of the three possibilities given by Dr. Dake for why people might continue to decline even after ccsvi venoplasty, that is why I responded at length about it.

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Cece wrote:If I recall, the Beirut study set the bar very high for what would be considered a stenosis. So actual stenoses did not get counted. Valve issues were excluded, missing jugulars were excluded.... So for the 12 out of 13 late RR MSers to be found to have ccsvi stenoses (by whatever name), they had to really have it to clear that high bar.

The doctors involved with the Beirut study did not "set the bar very high for what would be considered a stenosis." If you read the entire paper, you will see they exclude non-pathologic findings, and provide justification for doing so. How can a missing jugular have stenosis?

ccsvi stenoses (by whatever name)

This is not an insignificant point, since (1) not all vascular doctors agree that CCSVI is a pathologic condition, and (2) the "gold standard" of catheter venography is constantly emphasized, yet what is the criteria for diagnosing CCSVI with catheter venogram?

Some studies might have more false positives, some might have more false negatives. The Beirut study, by setting the bar too high and excluding stenoses that might have been included, would lean toward more false negatives. I was angry, as I recall, of how they set that up, since it was our first catheter venogram study. But I doubt it is the last. And in a study weighted toward false negatives, the positive findings of 12 out of 13 late RRMSers having CCVSI is valid.

That is your expert opinion that the study was weighted toward false negatives. But I don't see how you can criticize so soundly the methodology used in a study, then quote parts of the same study as proof of anything.

patientx wrote:The doctors involved with the Beirut study did not "set the bar very high for what would be considered a stenosis." If you read the entire paper, you will see they exclude non-pathologic findings, and provide justification for doing so. How can a missing jugular have stenosis?

I am surprised you can ask that question. The pathology is one of outflow obstructions. A missing jugular and a stenosed jugular both are outflow obstructions. No flow will go down either.

That is your expert opinion that the study was weighted toward false negatives. But I don't see how you can criticize so soundly the methodology used in a study, then quote parts of the same study as proof of anything.

If a study sets the bar high, it sets the bar high. I am not sure how else to describe that. I was unhappy that, with our first catheter venogram study, the bar was set unreasonably high. But at the same time, with those very high standards, 12 out of 13 late RRMSers had CCSVI. If they'd included missing jugulars or the other exclusions, perhaps 13 out of 13 late RRMSers would've been seen to have CCSVI, and a greater percentage of the early CISers too. The fact that I was not happy with what was excluded in no way negates what can be learned from those stenoses that were included.

In fact the reason I refer to the Beirut study is because the methodology was so stringent. It leaves little doubt that CCSVI existed in nearly every late RRMSer, as seen by gold standard catheter venogram.

patientx wrote:The doctors involved with the Beirut study did not "set the bar very high for what would be considered a stenosis." If you read the entire paper, you will see they exclude non-pathologic findings, and provide justification for doing so. How can a missing jugular have stenosis?

I am surprised you can ask that question. The pathology is one of outflow obstructions. A missing jugular and a stenosed jugular both are outflow obstructions. No flow will go down either.

A missing jugular does not present an obstruction - it is missing. Zamboni's original published cases were stenoses in exisiting veins. i don't recall he ever mentioned missing veins. His original theory was that these stenoses caused blood reflux, which led to leakage of red blood cells into brain tissue, which led to iron deposits, which caused an immune reaction against myelin tissue, etc, etc. A missing jugular vein wouldn't have reflux. Of course, now it seems CCSVI is defined as whatever one wishes it to be.

Do you have any other opinions on my opinions??

No, because your opinions on studies like this seem to be made without having read all of what the authors' wrote.

I don't understand all the arguing about this paper now. It is almost one year old, and was presented at the 2010 AAN conferences last April. It's old news. One year ago the science of CCSVI was a newborn. Now it's an infant. The research has moved far beyond this study by now, both pro and con.

Buffalo is poised to release several CCSVI studies in the near future. These should be telling…

Dr. Zamboni refers to agenesis, or the complete lack of a vein, in his endovascular treatment paper. He found it in the lumbar plexus of 18% of PPMS patients. It is considered a part of CCSVI, since it is a truncular venous malformation, and sadly, cannot be treated. A missing vein will lead to collateral and slowed circulation. We've seen a report (from Haacke) on a patient missing a jugular vein, who has MS. Hypoplasia, or really skinny, shoe string veins, are also truncular venous malformations.
link

The patency rate was also satisfactory for PTA treatment of azygous hypoplasia in ﬁve of six patients, yielding a cumulative patency rate of 96% at 18 months (Fig 7). In 12 patients, the AZY system presented stenoses at several points and even aspects of agenesis of the lumbar plexuses (18%). It is noteworthy that such presentation was signiﬁcantly associated with the PP course, with MS plaques distributed in the spinal cord.4 This malformation, of course, was not treated, probably explaining the worse results obtained in these patients with respect to the RR course.

And I don't see how the date on this affects its importance, especially since it was published in toto last week. Hypoperfusion was found in all pwMS who also had CCSVI. That's a pretty important correlation.
cheer

Complete lack of a vein is very unusual, Dr. Sclafani has suggested that it is talked about among us patients but very very rarely seen by the practitioners. Phelobologist in the doctor's thread mentioned having seen a patient with jugular agenesis. Also the Sardinian children seen by Dr. Zamboni early in his career who were treated for jugular phlebectasia by ligation of their jugulars, were they the children who grew up to have MS? Jugular ligation results in the same presentation as agenesis.

I agree that this paper is worth discussing. My neurologist claimed that the hypoperfusion in MS is a result of atrophy and lack of brain use and could have nothing to do with CCSVI. If hypoperfusion is being seen in patients with early MS and without atrophy, that seems a good rejoinder to that argument.

And the press finds this research newsworthy, since it will be discussed at the ISNVD this coming week in Bologna, Italy---for the first time the full study on the Americans and Italians will be discussed, and all the results on perfusion, SWI and disability will be presented by Dr. Zivadinov.

Here is the press in Ferrara, IT...via google translate--

Ferrara, 11 March 2011 - In support of the Zamboni method involved a study of Italian-American, published in 'BMC Medicine' in March, and demonstrates how the narrowing of the jugular veins are the blood flow slowly in the brain impacting on the genesis and progression of multiple sclerosis (view put forward by Professor Paolo Zamboni).

The results of the study will be presented at the conference organized by the 'International Society for neurovascular disease' in Bologna on 14 and 15 March under the patronage of the Presidency of the Republic.

The study and 'the fruit of a collaboration between the University Centre vascular disease' Ferrara directed by Zamboni, the old 'good' Bellaria Hospital in Bologna, directed by Fabrizio Salvi and the department of neurology and neuroimaging at the University 'New York, home to Buffalo, directed by Professor Robert Zivadinov.

I know of several international journalists that are covering this conference, so hopefully this research will be given a bit of coverage in the press. This research was not quickly published in the Annals of Neurology after three months of peer-review....but that does not mean it isn't important.
cheer

marc - this is a discussion .... not an argument . And some of us may have missed an important post .... what with all the information now coming fast and furious . So .... yeah .... I appreciate someone bringing up some past post. A year is not a long time.

And for the record .... I am as interested in posts / research papers that are not in agreement with the CCSVI theory, as with . As long as they are presented respectfully.

We now have at least TWO separate and independent [ Three .... counting Dr. Zamboni's original 65 pwMS trial ] medical teams that have preformed the CCSVI procedure on numerous pwMS and have now published papers .....telling us ..... this procedure is ... SAFE.

The question of using stents is yet to be answered . Is stenting safe ?

And finally . The biggest question of all ..... Does the treatment of CCSVI venoplasty result in positive symptom relief for pwMS ?

So far .... for some YES ....... for some No.

It's the YES ...... that is causing such a great excitement in the MS world.

I will ignore the discussion with the naysayer Lyon. He seeks to mislead anyone who wants factual info on CCSVI syndrome.

Early in this thread Ikulo and Cheerleader disagreed with my statement. Its worth considering the papers mentioned in full:

MarkW wrote:
The hypoperfusion may occur early or late in MS progression, no one knows.

Ikulo wrote:
..there have been a few studies noting hypoperfusion in MS as compared to severity of MS. Dr. Grossman has done incredibly fastinating radiological studies regarding this matter. Here is a quote from one of his papers:
Quote:
Compared to RR-MS, PP-MS patients showed significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in the periventricular and frontal NAWM (p values: 0.0029 and 0.022). EDSS was significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038, respectively)

MarkW - The whole paper is complex....... Towards the end of the discussion it states:
Further studies are warranted to better explore the relationship between clinical and perfusion measures and to establish the role of the molecular mechanisms causing MS-related neurodegeneration. In particular, longitudinal studies in patients in the earliest stages of the disease will have to establish whether hemodynamic impairment is a mediator or a marker of degenerative tissue.

Cheerleader added:
That's a great paper, Ikulo...
here's an entire thread on hypoperfusion. This was the reason I started on the vascular path in the first place. Dr. Haacke has some research coming out on perfusion as well. This is a trememndous piece of the MS puzzle.
http://www.thisisms.com/ftopict-7708.html

MarkW - The abstract says:
Hypoperfusion of the normal-appearing white matter in multiple sclerosis (MS) may be related to ischemia or secondary to hypometabolism from wallerian degeneration (WD). This study evaluated whether correlating perfusion and diffusion tensor imaging (DTI) metrics in normal-appearing corpus callosum could provide support for an ischemic mechanism for hypoperfusion.

Abstract finishes:
Thus, the purpose of this study was to evaluate the relationship between perfusion and DTI changes in the normal-appearing corpus callosa of patients with relapsing-remitting MS (RRMS), with the hypothesis that correlations between perfusion and DTI measures would be more consistent with what would be expected in primary ischemia.

The discussion says:
Numerous histopathologic and biochemical studies have demonstrated that in addition to the characteristic discrete white matter lesions found in patients with MS, there is diffuse abnormality involving grossly NAWM. Findings in the NAWM include decreased myelin-specific protein,1 diffuse astrogliosis,31 and infiltration by macrophages and T lymphocytes.3,4 Although MS has prototypically been characterized as a demyelinating disease, axonal damage, including axonal transection and decreased fiber attenuation, has been demonstrated in both lesions as well as within the NAWM.2,32

MarkW concludes:
Hypoperfusion is an interesting part of the MS jigsaw. It is too early to say it comes first in MS. I agree with the first paper 'longitudinal studies in patients in the earliest stages of the disease will have to establish whether hemodynamic impairment is a mediator or a marker of degenerative tissue'.

The neuros saw the immune system issues and concluded that MS was immune in origin. Let us not fall into the same trap with haemodynmic issues. MS is complex and multifactorial. Any theory on its etiology must explain the whole jigsaw not just part of it.

MarkW

Last edited by MarkW on Sun Mar 13, 2011 4:00 pm, edited 1 time in total.

Lyon wrote:In all seriousness, it's clear to everyone except the most hardened CCSVI zealots that the theory of CCSVI has started circling the drain.......I think "all over but the crying" is the correct term.

Lyon wrote:In all seriousness, it's clear to everyone except the most hardened CCSVI zealots that the theory of CCSVI has started circling the drain.......I think "all over but the crying" is the correct term.

Of course! That's why all those leading doctors are in Bologna right now! They must be just on vacation, hanging out, drinking espresso and eating pasta all day. It has nothing to do with so many of them dedicating their research to the topic of CCSVI.

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